Ovarian tumors I

OVARIAN TUMORS-I

Dr Aksharaditya ShuklaResident, Department Of Pathology

MGM Medical College & M.Y. Hospital, Indore

Dr Aksharaditya Shukla

Ovarian tumours

Tumour of the ovary are common form of neoplasia in women

Accounts for 3% of all cancers in females80% are benignMore common in older white women of

northern European ancestry90% of malignancies are carcinoma, 80%

have spread beyond the ovary at diagnosis.


Risk factors for carcinoma

NulliparityFamily historyChildhood gonadal dysgenesisClomipheneHereditary non polyposis colon cancerBRCA1 and BRCA2 mutationsCA-125 present in 80% of serous and

endometrioid tumoursCytogenetics-gain of 12 & 8loss of chr X,22 18,17,14,13,12 & 8 ,benign/borderline tumor exhibit trisomy12


Classification of ovarian tumours

Novak's classification (1967) has advantage of being simple but has certain obvious drawbacks, since it depends primarily on two fundamental factors; benign or malignant and solid or cystic.

Thus the borderline tumors, solid tumors with cystic degeneration and predominantly cystic tumors with solid areas fall into grey zone.


In 1971, the cancer committee of International Federation of Gynecology and Obstetrics (FIGO) proposed a histological classification of common primary epithelial ovarian tumors. Although this classification covered only epithelial tumors, it was a step in the direction of uniformity in classification and it also included the group of tumors of "low potential malignancy".

A significant stride in the direction of a histogenesis-based classification system was made in 1973 with the publication of the World Health Organization (WHO) Classification of Ovarian Tumors. This classification system was updated in 1999 and recently in 2003.


WHO classification of ovarian tumours

1. SURFACE EPITHELIAL TUMOURS2. GERM CELL TUMOURS3. SEX CORD STROMAL TUMOURS 4. GERM CELL SEX CORD STROMAL TUMOURS 5. TUMOUR OF THE RETE OVARII 6. MISCELLANEOUS TUMOURS 7. TUMOUR LIKE CONDITIONS8. LYMPHOID AND HEMATOPOETIC TUMOURS9. SECONDARY TUMOURS


1. Serous tumours2. Mucinous tumours 3. Endometroid tumours including variants of

squamous differentiation4. Clear cell tumours 5. Transitional tumours6. Squamous cell tumours 7. Mixed epithelial tumours 8. Undifferentiated and unclassified tumours.

SURFACE EPITHELIAL TUMOURS


¼ of all ovarian tumorsAdults30-50% bilateral60% benign,15%

borderline,25% malignantPapillary formation

presentM/E: cuboidal to columnar

cells lining wall of cysts and papillae

Psammoma bodies 30%

Serous tumors


BENIGNa) Cystadenoma b) Papillary cystadenomac) Surface papilloma d) Adenofibroma and cystadenofibroma BORDERLINEa) Papillary cystic

tumour b) Surface papillary

tumour.c) Cystadenofibroma

MALIGNANTa) Adenocarcinoma

b) Surface papillary

carcinomac) Adenocarcinofibroma

SURFACE EPITHELIAL TUMOURS (SEROUS TUMORS)


Cystic masses usually unilocular, containg clear but sometimes viscid fluid

Multiloculated smooth glistening cyst wall with no epithelial thickening or papillary

Serous cystadenoma- gross


Serous cystadenoma

Cuboidal to columnar cells are seen lining wall of the cysts and papillae in better differentiated tumors.


Borderline serous cystadenoma

Age:20-50yrs

Bilaterality-30%

Prognosis-100% 5yr survival

GROSS- increased

papillary projections within cyst


Borderline serous tumor.

Entirely increased complexity of stromal papilla with stratification and nuclear atypia.

But there is no

infiltrative growth into the stroma.


Epithelial stratification

(2-3 layers).

↑ complexity of stromal papillae.

No stromal invasion


Serous Cystadenocarcinoma

Age:40-70 yrBilaterality-

~66%Marker- CK7Prognosis-70% 5 yr survivalGROSS- - irregular

tumour mass - ↑ solid/

papillary - necrosis/

haemorrhage

Complex papillary architecture.

Malignant cells in glandular pattern.

Nuclear atypia.

High mitotic activity.

Stratification.

Stromal invasion

Serous Cystadenocarcinoma



Papillary serous cystadenocarcinoma of the ovary

. Microscopic features include stratification of low columnar epithelium liningthe inner surface of the cyst and a few psammoma bodies. The stroma shows invasion by clusters of anaplastic tumour cells.


Diagrammatic representation of general histologic criteria to distinguish benign, borderline (atypical proliferating) and malignant surface epithelial tumours of the ovary.


In some serous neoplasm fibroblastic stromal component is unduly prominent

Grossly as white , nodular foci in an otherwise cystic neoplasm

1. Benign (common) adenofibroma &

cystadenofibroma

2. Borderline

3. Malignant adenofibrocarcinoma

cystadenofibrocarcinoma


Ovarian cystadenofibroma

Well differentiated glands are embedded within a dense fibrous stroma


Benign surface papillomas

Intermediate borderline surface papillary tumors

Malignant serous surface papillary

tumors

Some serous neoplasms grow exophytically on the surface of ovary , with little involvement of underlying organ


Papillomatous outer surface of the ovary.

Minimal enlargement of the ovary.

Serous surface papillary carcinoma


Serous surface papillary carcinoma

There is hardly any infiltration of the stroma.

Mostly bilateral, highly aggressive, with peritoneal spread at the time of surgery.


Serous psammocarcinoma

A rare form of serous adenocarcinoma.

Involve ovarian surfaceMassive psammoma

body formation.Low grade cytologic

features. Abundant psammoma

bodies in at least 75% of the papillae.


Immunohistochemistry of serous tumors

keratin profile

CK 7+/ CK20-

Also CK8, CK18, CK19, EMA, S100

WT-1 stains diffusely most serous carcinomas


Ovarian implants

Deposits of ovarian tumours on peritoneal surface.

Entire peritoneum may contain tumour nodules<1 cm.

Seen in 1/3 patients with serous borderline and malignant tumours.

Affect prognosis.

Unencapsulated serous tumors of the ovarian surface are more likely to extend to the peritoneal surfaces


Less common. About 25%.

Bilateral 10%-20% (clonal).

80% are benign or borderline type.

MUCINOUS TUMORS


BENIGNa) cystadenoma b) adenofibroma and c) cystadenofibroma BORDERLINEa) intestinal type b) endocervical type MALIGNANT a) adenocarcinoma b) adenocarcinofibroma

MUCINOUS CYSTIC TUMOUR WITH MURAL NODULES

MUCINOUS CYSTIC TUMOUR WITH PSEUDOMYXOMA

PERITONEI

SURFACE EPITHELIAL TUMOURS (MUCINOUS TUMORS)


Mucinouscystadenoma

Larger then serousCysticMultiloculatedFluid is viscous

material of mucoid nature present.


Mucinous cystadenoma

These benign cysts are lined by a single layer of tall columnar mucinous epithelium without cilia.


Mucinous cystadenoma of the ovary.

The cyst wall and the septa are lined by a single layer of tall columnar mucin-secreting epithelium with basally-placed nuclei and large apical mucinous vacuoles.


Intestinal type (80%)

Endocervical type (20%)

Borderline mucinous tumors


Borderline mucinous cystadenoma

Age:40-70yr

Bilaterality- 5-10%

GROSS- -multiloculated cysts -papillae


Borderline mucinous tumor (intestinal type)

Epithelial lining with a “picket fence appearance”

Intestinal-type lining which may be several layers thick

Mild to moderate nuclear atypia is present

But destructive stromal invasion with an associated desmoplastic stromal response ABSENT

Goblet cells. Intestinal enzymes

lipase , trypsin) But No evidence of

hormone excess

Lining of mucinous cystadenoma


Borderline mucinous tumor(endocervical type)

Associated with endometriosis

Lining of tall non-ciliated cells

Basally located nuclei

Abundant intracellular mucin

Endocervical lined tumors are more likely to be bilateral and have associated peritoneal implants


Malignant Mucinous tumors

Age -40-70 yrs.Bilaterality- 5-15%.

The neoplasm is predominantly solid, but some mucin-containing cystic spaces can still be appreciated.

Thickened cyst wall.Areas of hemorrhage

and necrosis


Malignant Mucinous tumors

Cell atypiaIncreased layeringGland complexityPapillaeAreas of stromal invasion

Complex architecture and obvious nuclear atypia in mucinous cystadenoma


STROMAL INVASION in MUCINOUS TUMORS

Unquestionable carcinoma stromal invasion

Uncertain invasion . atypical epithelium < 4 cells thick - borderline

atypical epithelium > 4 cells thick - carcinoma


Primary ovarian carcinoma

Metastasis

UnilateralSize>10 cm

Smooth external surface

Expansile pattern of invasion

Complex papillary pattern

Without discrete nodularity

BilateralH/O extraovarian primary

mucinous adenocarcinomaSurface implantsInfilterative pattern of

stromal invasionNodular invasive patternOvarian hilar involvementVascular invasionPrimary sites-45%GI,20%

pancreas,

Mucinous cystadenocarcinoma primary Vs metastasis


Pseudomyxoma peritonei

Mucinous tumors (like serous tumors) may involve the peritoneal surface with collection of extensive mucinous material resembling cystic contents within the peritoneal cavity.

Is a rare condition Seen with primarily borderline or malignant

neoplasms. Major complication:

Extensive interadherence and adhesion of the viscera, producing a matting together of the abdominal contents and intestinal obstruction


Immunohistochemistry of Mucinous tumors

CEA EMA (particularly if

malignant) MUC5AC Dpc4 CK7+ (always) CK20+ (50 %)

Intestinal TypeImmunohistochemically

endocrine cells contain: 5-

hydroxytryptamine (serotonin)

ACTH gastrin somatostatin


1. Serous tumours2. Mucinous tumours Endometroid tumours including

variants of squamous differentiation3. Clear cell tumours 4. Transitional tumours5. Squamous cell tumours 6. Mixed epithelial tumours 7. Undifferentiated and unclassified tumours



ENDOMETROID TUMORS

10-25% of all primary ovarian carcinomas

Coexistent endometriosis in 10-20%

Grossly, endometroid carcinoma may present as cystic or solid mass

Contents are hemorrhagic

Visible papillary formations absent.

Good prognosis.


ENDOMETROID TUMORS

Villous papillary structures and/or tubular glands composed of a stratified layer of epithelial cells with smooth luminal borders.

Destructive stromal invasion is present.

Resembles appearance of endometrial carcinoma, with centrally placed nuclei.


ENDOMETROID TUMORAdenoacanthoma

Well-differentiated endometrioid ovarian carcinoma with extensive squamous metaplasia.

Foci of squamous metaplasia in 50%.

May be peritoneal keratin granulomas

Well-differentiated endometrioid ovarian carcinoma with extensive squamous metaplasia


Endometrioid (cyst) adenofibroma


Immunohistochemistry of endometroid carcinoma

Keratin

EMA

Vimentin

CEA usually negative or weak


1. Serous tumours2. Mucinous tumours 3. Endometroid tumours including variants

of squamous differentiationClear cell tumours 4) Transitional tumours5) Squamous cell tumours 6) Mixed epithelial tumours 7) Undifferentiated and unclassified tumours



Clear cell tumors Frequency- <5%.

Epithelial tumors of the ovary in which most or all of the cells have clear cytoplasm; most are malignant with rare benign and borderline variants.

Often associated with endometriosis and endometrial Ca.

The tumor is predominantly cystic mixed solid and cystic masses. But often contain mixed nodules.

Clear cell carcinomas are always high grade. Poor prognosis,


Growth patterns: tubular–cystic papillary solid sheet

Have abundant clear cytoplasm and significant nuclear atypia.

Clear cell tumor

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Clear cell tumors

Clear cell carcinoma of ovary. Note the high nuclear grade and the hobnail configuration

Tumor cells: large, Clear Nuclei: some protrude into lumina, resulting in hobnail

configuration ,cytoplasm: clear &often contains: Glycogen, mucin, fat,may be PAS-positive diastase-resistant hyaline

globules


Clear cell carcinoma

Clear cell carcinoma of ovary showing short papillae with hyalinized cores lined by highly atypical cells.


Clear cell carcinoma (oxyphilic variant) Clear cell adenofibroma


Special Stains and Immunohistochemistry of Clear cell

tumors

Hyaline globules negative for α-fetoprotein Tumor cells:

always reactive for: keratin (CK7, CK5/6, CAM

5.2 EMA CEA CD15 (Leu-M1) vimentin bcl-2 p53 CA-125

Variably reactive for: estrogen and

progesterone receptors: much greater expression of

ER than PR ER exclusively of β rather

than αtype HER2/neu α-fetoprotein

negative for: CK20

also reactive for: hepatocyte nuclear factor-

1β: transcription factor

involved with liver differentiation


1. Serous tumours2. Mucinous tumours 3. Endometroid tumours including variants

of squamous differentiation4. Clear cell tumours Transitional tumours5) Squamous cell tumours 6) Mixed epithelial tumours 7) Undifferentiated and unclassified tumours



Benigna) Brennerb) Metaplastic variantBorderline

brenner

(proliferating variant)

Malignant a) Transitional cell

carcinoma (non-Brenner type).

b) Malignant Brenner tumour

Transitional tumours


Brenner Tumor and Transitional Cell Carcinoma

Resemble those of transitional cell neoplasms of the urinary tract.

1–2% of all ovarian neoplasms.

Average age at presentation ≈50 years:

Sometimes signs of hyperestronism, such as postmenopausal uterine bleeding from endometrial hyperplasia.

* Slow rate of growth * Rarely ascites


Benign Brenner tumour

Grossly, these tumors have a white to tan-yellow whorled cut surface, but may show cystic spaces and calcification

unilateral firm May be associated with: mucinous cystadenoma exceptionally struma ovarii also transitional cell

tumors of urinary bladder


Brenner Tumor

Epithelial cells: solid and cystic nests Resemble transitional

epithelium(urothelium).

Surrounded by abundant stroma.

Cysts with eosinophilic fluid in a fibrotic stroma.

Tumour cells -oval nuclei, distinct nucleolus, longitudinal groove.

Brenner tumor of ovary showing solid and cystic epithelial cells embedded within fibrous tissue.


Metaplastic Brenner tumor

* Unduly prominent cystic formations.

* Florid mucinous changes.

* Papillary fronds and nuclear atypia absent.


Borderline Brenner tumor

Pattern of proliferating Brenner tumor with greater atypia (equivalent to grade I or II transitional cell carcinoma).

Stromal invasion cannot be demonstrated

Borderline Brenner tumor showing solid area with papillary formations, associated with a large cystic space


Borderline Brenner

papillary fronds nuclear atypia resemble pattern of

low-grade (I or II) transitional carcinoma of urinary bladder

Highly proliferating (borderline) Brenner tumor


Borderline Brenner tumor

Nuclei:

oval

Small but distinct nucleolus, longitudinal grooves

clear cytoplasm:

The epithelial nests of Brenner tumor are composed of cells with oval nuclei, many of which exhibit longitudinal grooves


Malignant Brenner tumor

Stromal invasion

Recognized mainly because of association with a typical benign, metaplastic, proliferating, or borderline component.

Areas of nuclear atypia.


Transitional cell carcinomas of ovary (non-brenner type)

(TCCs) of the ovary resemble other epithelial carcinomas with solid and cystic areas.

Closely resemble TCC of the bladder.

By definition, no Brenner tumor component is present.

Ovarian TCC is graded using the criteria for TCC of the urothelial tract.


TCC ovaryPapillary cores lined by stratified, cytologically atypical epithelium

Benign brenner component absentStratified malignant transitional epithelium


Special Stains and Immunohistochemistry of Brenner tumors and TCC

Cytoplasm of tumor cells: immunoreactive for: - keratin - EMA - CEA: + also in lumen of cysts * May contain: glycogen, mucin, lipid

Steroidogenic enzymes usually absent


Malignant Mixed Müllerian Tumor

Resembles grossly in every respect its more common uterine counterpart.

The neoplasm is large, variegated, solid and cystic, with hemorrhagic and necrotic areas

Gross appearance of malignant mixed müllerian tumor of ovary. The neoplasm is large, variegated, solid and cystic, with hemorrhagic and necrotic areas


Malignant Mixed Müllerian Tumor

Carcinomatous component

may appear:

Serous Endometrioid Squamous Clear cell (mesonephroid)

Sarcoma-like elements may have appearance of:

Chondrosarcoma (most common) Osteosarcoma Rhabdomyosarcoma Angiosarcoma

Malignant mixed müllerian tumor of ovary exhibiting heterologous foci in the form of bone and cartilage


Non-specific malignant stroma

Endometrioid component

Clear cell component

Homologous type


Malignant Mixed Müllerian TumorHeterogenous Type

Showing skeletal muscle and fibrous element.

Malignant mixed müllerian tumor of ovary exhibiting heterologous foci in the form of skeletal muscle


Special Stains and Immunohistochemistryof MMMT

Often hyaline droplets containing α1-

antitrypsin in cytoplasm of tumor cells.

Prognosis: Extremely poor.

Most reliable prognostic criterion is initial tumor stage Most tumors have already extended outside ovary at

surgery.


To be continue…

Presented By: Dr Aksharaditya ShuklaResident, Department Of Patholgy

MGM Medical College & M.Y. Hospital, Indore

Ovarian tumors I

Health & Medicine

Transcript of Ovarian tumors I